Connective Tissue Disease Flashcards
What are Connective Tissue Diseases?
Multisystem disorders that can cause organ pathology SLE Sjogrens Systemic Sclerosis Mixed Connective Tissue Disease Anti-phospholipid Syndrome
What is the proposed pathogenesis of SLE?
Defect in apoptosis –> increased cell death
Defective clearance of apoptotic cell debris –> persistence of antigen & immune complex production
Circulating immune complexes with antigens in various tissues
in small BVs: complement activation & inflammation
BMs of skin & kidneys
Environmental & genetic basis of SLE
UK : &S: Black»_space; white (however disease rarely reported in Africa)
40% concordance in MZ
F:M of SLE
F:M is 11:1 in childbearing years
onset age of SLE
after puberty - 20-30s
% of SLE cases in women
90%
Constitutional signs & symptoms of SLE
fever
fatigue
weight loss
Other typical signs & symptoms of SLE (there’s way too many)
arthralgia, myaliga, AVN maybe malar rash, photosensitivity discoid lupus, Raynaud's lupus nephritis lung haematological neuropsychiatric cardiac GI
Investigation of SLE
no one diagnostic test
FBC may show: anaemia, leucopenia, thrombocytopenia
urinalysis: look for glomerulonephritis
imaging: CT, MRI, Echo (organ involvement)
serology
Serology for SLE
ANA: high sensitivity, low specificity
Anti-dsDNA: varies with disease activity (so may not be super sensitive), high specificity
Anti-Sm: low sensitivity, high specificity
C3/4: sensitivity low when disease is active
Specific disease markers for SLE
Anti-dsDNA, Anti-Sm
ANA not specific
Sensitive disease markers for SLE
ANA very sensitive (not specific though)
Anti-dsDNA varies with disease activity
(Anti-Sm low sensitivity)
Which marker is used for disease activity in SLE
Anti-dsDNA
Which marker is used for disease activity in SLE
Anti-dsDNA
SLICC classification criteria for SLE
4 or more criteria with at least 1 clinical & 1 laboratory
or biopsy-proven lupus nephritis with positive ANA / Anti-DNA
Clinical Criteria for SLE (11)
Acute Cutaneous Lupus Chronic Cutaneous Lupus Oral / Nasal Ulcers Non-scarring alopecia Arthritis Serositis Renal Neurologic Haemolytic anaemia Leukopenia Thrombocytopenia
Immunologic Criteria for SLE
ANA Anti-DNA Anti-Sm Antipohspholipid Ab Low complement (C3,4) Direct Coomb's test
Treatment of SLE of there is skin disease & arthralgia
hydroxychloroquine
topical steroids
NSAIDs
Treatment of SLE if there is inflammatory arthritis/ evidence of organ involvement (pericardial disease, ILD)
immunosuppression: azathioprine /myocephanolate mofetil
Corticosteroids at moderate doses for short periods
Treatment of SLE if there is severe organ disease (lupus nephritis / CNS lupus)
IV steroids, cyclophosphamide
Treatment of unresponsive SLE
IV immunoglobulin, rituximab
Monitoring of SLE
according to symptoms
check regularly: Anti-dsDNA, C3/4
urinalyiss- check for glomerulonephritis
evaluate & manage CV risk factors - BP, cholesterol
What is the pathogenesis of Sjogrens Syndrome?
Autoimmune - lymphocytic infiltrates in exocrine organs
Aetiology of Sjogrens Syndrome:
Primary
Secondary to other AI - RA, SLE
Symptoms of Sjogrens Syndrome
sicca symptoms: dry eye & mouth
other symptoms: arthralgia, fatigue, vaginal dryness, parotid gland swelling
may also occur: peripheral neuropathy & ILD, increased risk of lymphoma
Diagnosis of Sjogrens Syndrome
4 of the following:
occular symptoms:
-dry eyes for > 3 months
-foreign-body sensation
-use of tear substitutes > 3x/day
oral symptoms:
-dry mouth
-recurrently swollen salivary glands
-frequent use of liquids to aid swallowing
ocular signs
-Schimer test without anaesthesia (<5mm in 5min)
-positive vital dye stainint result
oral signs
-abnormal salivary scintigraphy findings
-abnormal parotid gland scintigraphy findings
-abnormal sialometry findings
-unstimulated salivary flow <1.5 mL in 15 min
positive minor salivary gland biopsy findings
positive anti-SSA/anti-SSB (Ro or LA)
Serology in Sjogrens Syndrome
Anti-SSA/Anti-SSB (Ro / LA)
Oral Symptoms & Signs of Sjogrens Syndrome
Symptoms: -dry mouth -recurrent swollen salivary glands -frequent use of liquids to aid swallowing Signs: -abnormal salivary scintigraphy findings -abnormal parotid scintigraphy findings -abnormal sialometry findings -unstimulated salivary flow <1.5 mL in 15 min
Oral Symptoms & Signs of Sjogrens Syndrome
Symptoms: -dry mouth -recurrent swollen salivary glands -frequent use of liquids to aid swallowing Signs: -abnormal salivary scintigraphy findings -abnormal parotid scintigraphy findings -abnormal sialometry findings -unstimulated salivary flow <1.5 mL in 15 min
What is the Pathogenesis of Systemic Sclerosis
Excessive Collagen Deposition leading to skin & internal organ changes
Vasomotor disturbances (Raynaud’s)
Fibrosis
–> Atrophy of skin & subcutaenous tissue
3 phases of cutaneous symptoms: odematous, indurative, atrophic
3 phases of cutaneous symotoms of SSC
odematous
indurative
atrophic
What leads to death in SSC?
renal & lung changes
pulmonary hypertension leads to 12% of SSC-related deaths
Signs & Symptoms of SSC
Raynaud's phenomenon Thickened & Tight skin -skin of face: pinching of the skin of nose (beaking) -tightening of the skin around the mouth Telangiectasia Calcinosis - may be seen in digits
Major & Minor Features of SSC
Major: -centrally located skin sclerosis -arms, face, neck Minor: -sclerodactyly & atrophy of fingertips -bilateral lung fibrosis
Organ involvement in SSC
lung: pulmonary HTN, pulmonary fibrosis
accelerated HTN –>
renal crisis
gut: dysphagia, malabsorption, bacterial overgrowth of small bowel
MSK: inflammatory arthritis & myositis
Limited SSC other name
CREST
Limited SSC disease progression
skin involved confined to face, hands, forearms & feet
organ involvement occurs later
Diffuse SSC disease progression
skin changes develop more rapidly, can involve the trunk
early significant organ involvement
Limited SSC Ab
Anti- Centromere
Diffuse SSC Ab
Anti-Scl-70
Investigations of SSC
Immunology Organ screening regularly: -pulmonary function test, -echocardiogram, -monitor renal function
Diagnosis of SSC
1 major & 2 minor features
Major features of SSC
centrally located skin sclerosis
arms, face, neck
Minor features of SSC
sclerodactyly and atrophy of the fingertips
bilateral lung fibrosis
Treatment of SSC
Raynauds/digital ulcers: CCBs (Iloprost, Bosentan)
Renal involvement: ACEi
GI involvement: PPI for reflux
ILD: immunosuppression - cyclophosphamide
Features & Symptoms of MCTD
Raynauds Arthralgia/Arthritis Myositis Sclerodactyly Pulmonary HTN ILD
Serology for MCTD
anti-RNP Ab
Monitoring of MCTD
Regular echocardiograms - risk of pulmonary htN
Pulmonary function test - screen for ILD
Treatment of MCTD
Depends on presentation
Raynauds: CCBs (Iloprost, Bosentan)
Muscle/lung disease: immunosuppression
What is the pathology behind Anti-Phospholipid Syndrome?
Recurrent venous/arterial thrombosis and/or fetal loss
Associated diseases to Anti-Phospholipid Syndrome
SLE or other AI disorders
Signs & Symptoms of Anti-Phospholipid Syndrome
- Increased frequency of stroke/MI
- Recurrent pulmonary emboli/thrombosis - pulmonary HTN
- Catastrophic ACS (CAPS): multiorgan infarction over a period of days-weeks
- Late spontaneous fetal loss (2nd or 3rd trimester)
- Recurrent early fetal loss (10 weeks) also possible
- Migraine
- Livedo reticularis
In Anti-Phospholipid Syndrome, what is stroke due to?
In situ thrombosis
Embolization origination from the valvular lesions of Libman-Sacks (Sterile) Endocarditis
What is a common cutaneous finding in APS?
Livedo Reticularis
Investigations of APS
Thrombocytopenia
Prolongation of APTT
Immunology
Serology of APS
Lupus ANticoagulant
Anti-cardiolipin
Anti-beta 2 glycoprotein
Treatment of APS
episode of thrombosis: Anti-coagulation
recurrent pregnancy loss: LMWH during pregnancy (Warfarin would be teratrogenic)
Positive Ab without thrombosis event: don’t require anticoagulation
